Key points

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  Fossa ovalis is a depression on the right atrial side of interatrial septum. It is an embryonic remnant of a once patent channel between the right and left atria of the fetal heart, serving fetal circulatory system. In adults, this landmark is often used surgically for accessing the left atrium from right atrium for various surgical procedures.

  
  
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  In about a quarter of the population, this channel fails to close leading to patent foramen ovale. This foramen is implicated in various pathologies like paradoxical thromboembolism leading to conditions like cryptogenic stroke. This patency may also be associated with atrial septal aneurysm, that increases the risk for associated pathologies. Patent foramen ovale can be diagnosed using transesophageal echocardiography with bubble study, and transthoracic echocardiography, among other radiological techniques. Management involves percutaneous closure of the foramen ovale using occluder devices.

  
  
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  Cardiac masses can range from simple cardiac growths to benign cardiac tumors and malignant neoplasms. Management involves resection of most tumors depending on their size and severity of the associated symptoms.

Morphology

The fossa ovalis is a three-dimensional structure consisting of the septum itself and the annulus or limbus fossa ovalis, the raised edge around the perimeter of the fossa . The annulus gives the margins of the fossa a crater-like appearance. Although there is a wide variation in the location and geometry of the fossa ovalis, structurally, the fossa can vary from being smooth to a net-like formation. The fossa can also be patent or form a right-sided pouch (RSP) . The RSP may imitate a PFO channel. The shape of the fossa is oval in most people .

Anatomical relations

The septum that separates the right atrium from the left atrium has an oval thumbprint size depression called the fossa ovalis on the lower portion of its right atrial side. It has a prominent margin, the limbus fossa ovalis (border of the oval fossa). The fossa lies cephalad and left of the inferior vena cava, and the coronary sinus lies caudal and anterior to the fossa, whereas His bundle shares the same horizontal plane with the fossa ovalis ( Fig. 28.2 ). The depression in the fossa represents the residuum of the embryonic oval foramen and its valve—important components of the fetal circulation. The interatrial septum faces forward and to the right, corresponding to the location of left atrium that lies posteriorly and to the left of right atrium. The interatrial septum forms the anterior wall of the left atrium.

Fossa ovalis on the interatrial septum as seen through the right atrium.

Reproduced with the permission of Alamy, alamy.com (Public domain).

Anatomic relations of fossa ovalis.

Reproduced with permission from Clinical Anatomy Associates, Inc.

Surgically, the fossa ovalis, along with the midseptal region, represents the true interatrial septum and comprises only 20% of the entire interatrial septum. The fossa ovalis and this midseptal region are the only places where one can penetrate and create an interconnection between the two atria without exiting the heart .

Embryology

In the primitive atrium of the fetal heart, two partially muscular embryonic structures called septum primum and septum secundum fuse to form the interatrial septum ( Fig. 28.3 ).

Embryonic formation of fossa ovalis. (A) Ostium primum in septum primum. (B) Septum primum growing caudally toward the atrioventricular mesenchymal complex. (C) Formation of ostium secundum in septum primum, and formation of septum secundum. (D and E) Formation of foramen ovale.

Reproduced with permission from Cruz-González I, Solis J, Inglessis-Azuaje I, Palacios IF. Patent foramen ovale: current state of the art. Rev Esp Cardiol. 2008;61(7):738–751.

The ostium primum in the septum primum serves the purpose of shunting oxygenated blood from the umbilical vein through inferior vena cava and right atrium directly to the left atrium, bypassing the pulmonary system and the nonfunctional fetal lungs. Oxygen-rich blood hence shunts directly into the systemic circulation, a process necessary for the normal expansion of left atrium and left ventricle.

During the 4th week of fetal life, as the septum primum grows, the evolving atrioventricular mesenchymal complex begins to fill the gap in the interatrial connection of ostium primum ( Fig. 28.3 A and B). At the same time, as the ostium primum is gradually disappearing, new tiny perforations are created in the central region of septum primum by programmed cell death; those coalesce to form a new foramen called the ostium secundum ( Fig. 28.3 C), which is purposed for continued right to left shunting of blood before ostium primum finally closes.

Around 5–6 weeks, a second ridge called septum secundum begins to grow craniocaudally and dorsoventrally, overlapping the ostium secundum ( Fig. 28.3 D and E). This muscular ridge leaves an opening near the floor of the right atrium, forming the foramen ovale.

The cranial part of the septum primum, initially attached to the roof of the left atrium, gradually disappears ( Fig. 28.3 E). The remaining part of the septum, attached to the fused endocardial cushions, forms the flap-like valve of the foramen ovale. This valve prevents the backflow of blood away from the left atrium by collapsing against the stiff septum secundum. This shunt continues for the rest of the fetal development during the intrauterine life.

Functional closure of the foramen ovale

After birth, as the lungs become functional with neonatal breathing, the pulmonary vasculature abruptly dilates. This, combined with the cessation of umbilical flow, reverses the pressure difference, significantly decreasing the pressure in right atrium compared to the left. Increased pressures in the left atrium push the flexible septum primum (valve of the foramen ovale) against the more rigid septum secundum, even during atrial diastole, thus leading to functional closure of the foramen ovale.

Anatomical closure of the foramen ovale

Anatomical closure is achieved at around 3rd month when tissue proliferation and adhesion of the septum primum to the left margin of the septum secundum are complete, obliterating the foramen ovale.

As a result, the interatrial septum becomes a complete partition between the atria in about 75% of humans, carrying the memory of fetal foramen ovale as a depression, called the fossa ovalis. The septum primum forms floor of the oval fossa. The inferior edge of the septum secundum forms a rounded fold, the border of the oval fossa (limbus fossa ovalis), which marks former boundary of the foramen ovale, giving it a crater-like appearance.

Vascular supply

Right and left coronary arteries give off right and left anterior and posterior atrial branches, which anastomose to form Kugel’s artery or the arteria anastomotica auricularis magna ( Fig. 28.4 ) which supplies the interatrial septum.

Coronary angiogram of the right coronary system in the right anterior oblique view showing anomalous vessel connection (Kugel’s artery) between the proximal RCA and distal RCA ( red arrow ), also demonstrating CTO of mid-RCA. CTO , complete total occlusion; RCA , right coronary artery.

Reproduced with permission from Narh JT, Choudhary KV, Okunade A, et al. Kugel’s artery: silent bystander or savior? Cureus 2021;13(8):e17039. https://doi.org/10.7759/cureus.17039 .

The midportion of the interatrial septum, together with the fossa ovalis, receives the least amount of vascular supply. The number and density of these vessel networks also decreases with age. In the antero-inferior part of the septum, a comparatively dense vascular network exists .

Nerve supply

Angiotensinergic (renin–angiotensin–aldosterone dependent) innervation dominates the right atrium, which might also be a source of angiotensin II. It modulates autonomic nervous function in the heart thereby facilitating presynaptic noradrenaline release. Vagal efferents and noncatecholaminergic afferents comprise the peripheral nerve fibers, a small amount of whose impact is sympathetic.

Use of fossa ovalis as a surgical plane

For most surgical procedures that require access from the right atrium to the left heart chambers, the (limbus) fossa ovalis represents the most direct anatomical landmark and avenue of access ( Fig. 28.5 ). Situations requiring such access include hemodynamic assessment of the mitral valve, catheter-based mitral valve repair, paravalvular leak closure, and percutaneous balloon valvuloplasty. Left atrial appendix closure, pulmonary vein isolation, and radiofrequency catheter ablation also make use of the true interatrial septum formed by the fossa ovalis for transseptal puncture. In the presence of a prosthetic aortic valve, the fossa ovalis provides an alternate access to the left ventricle besides the retrograde route through the aortic valve. PFO and ASD repair also makes use of the same fossa landmark for access.

Right heart catheter traversing through fossa ovalis to enter the left heart.

Reproduced with permission from Babaliaros VC, Green JT, Lerakis S, Lloyd M, Block PC. Emerging applications for transseptal left heart catheterization: old techniques for new procedures. J Am Coll Cardiol. 2008;51(22):2116–2122.

Change of morphology of fossa ovalis in certain conditions

Patent foramen ovale

Incidence and morphology

In about 25%–35% of the population, the fetal foramen ovale fails to close, leaving a patency between the right and left atria known as the “patent foramen ovale.” It is not a true defect of the interatrial septum like the atrial septal defects, rather a variant of fossa ovalis occurring due to the failure of successful fusion of the septum primum and secundum . There is variation in the location and size of the fossa ovalis from heart to heart ; therefore, a corresponding variation is seen in the corresponding characteristics of the patent foramen ovale. In most cases, the height of the curvilinear, oblong tunnel-like patent foramen ovale ranges anywhere between 1 and 6 mm and width between 5 and 13 mm along the curve of the muscular rim formed by septum secundum, with a diameter of 1–10 mm. The size tends to increase with increasing age .

Antero-superiorly, the right atrial entrance of patent foramen ovale is bordered by the muscular rim of the fossa, whereas the thin flap valve forms the posterior border. A crescentic free edge of the embryonic septum primum forms the left atrial entrance . This entrance is in proximity to the left atrial antero-superior wall and is of surgical importance while advancing a catheter due to the risk of exiting the heart as this part of the left atrial wall is exceptionally thin ( Fig. 28.6 ).

Patent foramen ovale shown in autopsy specimen from a 85-year-old man. (A) Right atrial (RA) view shows a probe in foramen ovale, between limbus and valve (V) of fossa ovalis. (B) Left atrial (LA) view shows same probe as in (A) exiting through ostium secundum, the prominent fenestration in the valve. Normally, when left atrial pressure exceeds right atrial pressure, the valve of the fossa ovalis is pressed against the limbus and thereby closes the foramen ovale. IVC , inferior vena cava; MV , mitral valve; SVC , superior vena cava; TV, tricuspid valve .

Reproduced with permission from Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. 1984; 59(1 ):17-20.

Clinical pathology

Patent foramen ovale, atrial septal aneurysm, paradoxical embolism, and cryptogenic stroke

Paradoxical embolism

Patent foramen ovale (PFO), although benign on its own, is usually too small to be hemodynamically significant. However, even a small patent foramen can provide a channel for thrombi, fat particles, and gas bubbles to enter the systemic circulation, bypassing the pulmonary arterial circuit. This right to left shunting of the embolus via PFO, called “paradoxical embolism” ( Figs. 28.7 and 28.8 ), has been long associated with cryptogenic stroke, especially in a younger population without risk factors for ischemic stroke. In fact, out of all individuals who suffer cryptogenic stroke, nearly half harbor a PFO .

Paradoxical embolism, intraoperative demonstration of the large thrombus traversing the patent foramen ovale ( arrows ). View is taken through the open right atrium, while on cardiopulmonary bypass. The patient is a young male graduate student who was working for 9 weeks on his PhD thesis dissertation, essentially never leaving his desk during that time. He developed chest pain and severe shortness of breath, prompting his presentation to the emergency room. Despite the massive venous thrombus (see also Fig. 28.7 ), he recovered completely postoperatively and achieved his PhD degree shortly thereafter.

Published with permission from Koullias G, Elefteriades JA, Wu I, Jovin I, Jadbabaie F, McNamara R., Massive paradoxical embolism caught in the act. Circulation 2004;109:3056–3057.

Paradoxical embolism, intraoperative schematic reconstruction of the location of the massive volume of thrombotic material “caught in the act” of traversing the patent foramen ovale ( arrows ) into both the right and left pulmonary arteries.

Reproduced with the permission from Koullias G, Elefteriades JA, Wu I, Jovin I, Jadbabaie F, McNamara R., Massive paradoxical embolism, caught in the act, Circulation 2004;109:3056–3057.

Atrial septal aneurysm

Atrial septal aneurysm (ASA), although rarely an isolated abnormality, is frequently associated (50%–89%) with PFO . Presenting on echocardiography as a focal bulge of the IAS with displacement toward the left or right atrium , atrial septal aneurysm has been implicated as a source of cardiogenic emboli from thrombi formed by the stagnation of blood in the depth of its recess . Atrial septal aneurysm has also been known to develop fibrosis of its wall. An associated preexisting ASD can provide the patent connection permitting left atrial to right atrial intracardiac shunting, with all of its associated consequences. Elevated intracardiac pressures secondary to cardiac pathologies (and increased left atrial pressures) are likely to be involved in the formation of ASA .

A Chiari network, a fine, net-like latticework of residual atrial tissue, can serve as a nidus for thrombi to form, potentially leading to paradoxical embolization via a patent foramen ovale (see Fig. 28.9 ).

The Chiari network.

Reproduced with permission from Wikipedia ( www.wikidoc.org/index.php/Chiari_network ).

One can easily picture how an ASA full of thrombus, oscillating (hypermobile) right and left during the cardiac cycle, could easily displace systemic emboli, resulting in initially cryptogenic stroke ( Fig. 28.10 ).

Transthoracic echocardiogram (subcostal view) showing the atrial septal aneurysm ( red arrows ) bulging from the left atrium into the right atrium. Note the hyperechoic area within the atrial septal aneurysm suggestive of thrombus.

Reproduced with permission from Aryal MR, Pradhan R, Pandit AA, Polinsky R. A “Teapot” atrial septal aneurysm with spontaneous thrombus in an asymptomatic patient, 2013. Circulation 2013;128:e409–e410.

Other than associated ASA, certain morphologic features of the PFO confer high risk for causing pathology. These include large size (≥ 2 mm in height) and long tunnel (≥ 10 mm in length) of the PFO, prominent Eustachian valve, and large right-to-left shunt seen on echocardiography at rest and during Valsalva maneuver . Also included in the list is low-angle PFO (≤ 10 degree of PFO angle from the inferior vena cava longitudinal orientation) .

It is absolutely essential that individuals with otherwise unexplained embolic stroke undergo an echocardiogram with bubble study. The origin of the embolic material may often be ascertained by this simple, noninvasive study.

Decompression sickness and gas embolism

Decompression sickness (DCS) is caused by the supersaturation of blood and tissues with dissolved gases caused by breathing under high pressure, with subsequent evolution of gas bubbles as the pressure decreases when a diver rises toward the surface. These gas bubbles embolize from a pulmonary or intravascular origin into the arterial circulation, causing occlusion of a distal systemic arterial locus, leading to symptomology of cutis marmorata and vestibular and neurological DCS . PFO has been implicated to provide a channel for gas embolism to move from venous to arterial circulation via paradoxical embolism, especially in unprovoked and “undeserved” decompression sickness, where diving has been done within accepted safety limits .

Migraine

About half of the population suffering the symptoms of migraine headache with or without aura have a demonstrable concomitant PFO. A causal relation has so far not been established, but it is hypothesized that hypoxemia (via right to left shunting) or shunting of vasoactive chemicals (e.g., serotonin) which are ordinarily metabolized during their passage through the lungs, may be the cause of migraine headaches in patients with the right to left atrial shunt .

Platypnea–orthodeoxia syndrome

Patent foramen ovale is also known to cause platypnea–orthodeoxia syndrome (POS), a rare condition presenting itself as orthostatic arterial desaturation and hypoxia. As such, a drop in PaO ₂ > 4 mmHg or Sao ₂ > 5% from supine to an upright position characterizes the syndrome. This positional change in oxygen saturation has been attributed to the mixing of the deoxygenated venous blood with the oxygenated arterial blood via a shunt in the heart chambers or an arteriovenous malformation in the pulmonary circuit. Interatrial shunt via PFO is the most common cause of platypnea–orthodeoxia .

Fat embolism syndrome

PFO has also been implicated in paradoxical fat embolism syndrome (FES) in cases of traumatic bone fractures . This is of special consideration for orthopedic trauma surgeons .

Miscellaneous pathologies

PFO, especially with high-risk morphology, coupled with multiple gestation and hypercoagulability, poses increased risk of stroke, pulmonary emboli, and myocardial infarction in pregnant women . It is also hypothesized that the increased intrathoracic pressure during labor may lead to shunting of the blood from right to the left atrium in the presence of a PFO. In such cases, an amniotic fluid embolus may cause multiple cerebral infarcts using this channel to enter the systemic circulation .

It is also implicated in a minute number of acute myocardial infarctions by way of paradoxical embolism via interatrial communication . The presence of a PFO has been implicated in both air embolism and thromboembolism in the setting of liver transplant surgery .

Diagnosis

Transesophageal echocardiography

Transesophageal echocardiography (TEE) with bubble study offers the benefit of relative lack of invasiveness while providing high accuracy for determining the presence and anatomic characteristics of a PFO, including size, all the while differentiating PFO from other atrial septal defects and intrapulmonary vascular shunts (e.g., pulmonary arteriovenous malformations). For this reason, TEE is the standard for diagnosing a PFO . The significance of the shunt through a PFO is often estimated as a function of the degree of bubbles directly visualized passing from right to left atrium ( Fig. 28.11 ). This is best assessed using the bicaval view.

Transesophageal echocardiogram with positive bubble study through a patent foramen ovale.

Reproduced with permission from Mojadidi MK, Gevorgyan R, Tobis JM. A comparison of methods to detect and quantitate PFO: TCD, TTE, ICE and TEE. In: Amin Z, Tobis J, Sievert H, Carroll J, editors. Patent foramen ovale. London: Springer; 2015. https://doi.org/10.1007/978-1-4471-4987-3_7 .

Furthermore, the sensitivity and specificity of TEE can be increased using:

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  A provocation maneuver, with Valsalva or inferior vena cava (IVC) compression .

  
  
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  Unloading the left ventricle with nitroglycerin, thus dropping left-sided pressure and promoting leftward bulging of the interatrial septum, by reversing the interatrial pressure gradient, thereby reducing the number of false negative TEEs and eliminating the need for Valsalva in sedated patients.

  
  
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  Use of at least five contrast injections for enhanced visualization of dense right atrial contrast filling along with the leftward bulging of the interatrial septum .

  
  
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  Use of harmonic imaging mode for bubble studies performed with echocardiography, resulting in a higher yield for the detection of a PFO compared to fundamental imaging .

  
  
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  Addition of the patient’s blood to agitated saline mixture to enhance sensitivity of bubble studies without compromising specificity when compared to agitated saline alone and other contrast agents .

Transthoracic echocardiography

Transthoracic echocardiography (TTE) has a fairly low sensitivity (about 46%), with drastic improvement (of up to 90%) when performed with harmonic imaging ( Fig. 28.12 ).

Transthoracic echocardiographic imaging of a large waving tubular right atrial and left atrial thrombus through a patent foramen ovale (PFO).

Reproduced with permission from Koullias G, Elefteriades JA, Wu I, Jovin I, Jadbabaie F, McNamara R, Massive paradoxical embolism caught in the act. Circulation. 2004;109:3056–3057.

Current application

In cases of a suspected cryptogenic stroke, most healthcare centers prefer initial screening with TCD followed by echocardiography for the diagnosis of PFO . An isolated PFO for any suspected pathology is generally followed up initially with a TTE due to lack of invasiveness, although a TEE may be required for a definitive diagnosis. A PFO can be differentiated from an ASD as a PFO takes a tunneled intraseptal course. Presence of a flap valve on the left atrial side of the foramen is another indicator of PFO. Echocardiography also represents the best method of visualizing fossa ovalis membrane aneurysms in patients suspected to have cardiogenic emboli, although the emboli may arise from a different source .

Management

Most patients with an isolated finding of a PFO without associated pathology require no special treatment. When a PFO manifests pathology (embolization), a choice must be made between medical and surgical management.

Interventional management

Percutaneous closure of the patent foramen ovale with occluder devices ( Fig. 28.13 ) has been the mainstay of interventional management of PFO-related embolization as well as their prevention. Traditionally, PFO closure used to be done with open heart surgery. Over the past 4 decades, percutaneous catheter-based closure of the PFO has offered efficacy while sparing the invasiveness of open heart surgery.

Use of occluder device for closure of the patent foramen ovale (PFO).

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